Eosinophils play a deleterious role in recovery after major lung resection as a result of iNOS-mediated damage.
Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B559
Abstract ID: 4105
Presenting Author:
May A. Khalil , Research Associate at Univ. of Maryland Sch. of Med.
Abstract:
Pulmonary complications arise in nearly 50% of lung surgery patients. Little is known about the systemic stress response post-thoracic surgery. Using a murine model of right pneumonectomy, along with peripheral blood sampling from human patients, we noted a selective increase in eosinophils post-lung resection. Based on this, we tested the hypothesis that deleterious effects after lung resection are due to eosinophil activation using a conditional KO eosinophil-deficient mice strain with diphtheria toxin (DT) receptor expression on an eosinophil peroxidase-specific promoter (iPHIL). Eosinophil depletion in DT-treated iPHIL mice improved survival, recovery, oxygenation, and pulmonary edema compared to wild-type littermates. Since nitric oxide produced by inducible nitric oxide synthase (iNOS) contributes to pulmonary damage in several models such as sepsis, we evaluated the expression of iNOS in the left lung post-right pneumonectomy. We noted that Siglec-F+CD11bhi eosinophils expressed the highest levels of iNOS. Both genetic (iNOS KO mice) and pharmacological (N(gamma)-nitro-L-arginine methyl ester (L-NAME)) inhibition of iNOS improved survival following right pneumonectomy. In addition, we saw an increase in nitrosylation of the lung parenchyma in eosinophil-sufficient mice post-lung resection. Our findings suggest that repurposing clinically available eosinophil-targeting biologics could significantly improve outcomes of high-risk surgical patients post-lung resection.
Eosinophils play a deleterious role in recovery after major lung resection as a result of iNOS-mediated damage
Category
Poster and Podium (Block Symposium)